ArticleAnnals of neurology2016
Genetic variants in CETP increase risk of intracerebral hemorrhage.
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Article in Annals of neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.
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28citing papers in PubMed, 2 pooled it
3.0field-weighted citation impact, top 9% of its field
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Who cites it
28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 43 citations in OpenAlex.
- Genetic risk of Spontaneous intracerebral hemorrhage: Systematic review and future directions.Journal of the neurological sciences · 2019Pooled it
- Association of Apolipoprotein E With Intracerebral Hemorrhage Risk by Race/Ethnicity: A Meta-analysis.JAMA neurology · 2019Pooled it
- CD36 Gene Polymorphisms Are Associated with Intracerebral Hemorrhage Susceptibility in a Han Chinese Population.BioMed research international · 2017Trial
- Genetics of intracerebral hemorrhage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and cognitive impairment in middle-aged and elderly Chinese population.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- Precision acute medical care through "-omic" analyses: a scoping review.Personalized medicine · 2025Article
- U-shaped Relationship between high-density lipoprotein cholesterol levels and intracranial aneurysm rupture: a retrospective cross-sectional study in the Chinese population.BMC neurology · 2025Article
- Association of the COL4A2 Gene Polymorphisms with Primary Intracerebral Hemorrhage Risk and Outcome in Chinese Han Population.Molecular neurobiology · 2024Article
- Cerebral small vessel injury in mice with damage to ACE2-expressing cerebral vascular endothelial cells and post COVID-19 patients.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Association ofInternational journal of molecular sciences · 2024Article
- Very high high-density lipoprotein cholesterol may be associated with higher risk of cognitive impairment in older adults.Nutrition journal · 2024Article
- Article
- Genetically predicted on-statin LDL response is associated with higher intracerebral haemorrhage risk.Brain : a journal of neurology · 2022Article
- Intracerebral Hemorrhage Genetics.Genes · 2022Review
- Genetics and Epigenetics of Spontaneous Intracerebral Hemorrhage.International journal of molecular sciences · 2022Review
- Association of Lipids, Lipoproteins, and Apolipoproteins with Stroke Subtypes in an International Case Control Study (INTERSTROKE).Journal of stroke · 2022Article
- Genetics of Spontaneous Intracerebral Hemorrhage: Risk and Outcome.Frontiers in neuroscience · 2022Review
- Human Galectin-7 GeneFrontiers in molecular neuroscience · 2022Article
- Genetically Elevated LDL Associates with Lower Risk of Intracerebral Hemorrhage.Annals of neurology · 2020Article
- Genetic determinants of blood lipids and cerebral small vessel disease: role of high-density lipoprotein cholesterol.Brain : a journal of neurology · 2020Article
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Authors and funding
60 authors at 20 institutions in 11 countries.
Christopher D AndersonCenter for Human Genetic Research, Massachusetts General Hospital (MGH), Boston, MA.
Guido J FalconeCenter for Human Genetic Research, Massachusetts General Hospital (MGH), Boston, MA.
Chia-Ling PhuahCenter for Human Genetic Research, Massachusetts General Hospital (MGH), Boston, MA.
Farid RadmaneshCenter for Human Genetic Research, Massachusetts General Hospital (MGH), Boston, MA.
H Bart BrouwersCenter for Human Genetic Research, Massachusetts General Hospital (MGH), Boston, MA.
Thomas W K BatteyCenter for Human Genetic Research, Massachusetts General Hospital (MGH), Boston, MA.
Alessandro BiffiCenter for Human Genetic Research, Massachusetts General Hospital (MGH), Boston, MA.
Gina M PelosoCenter for Human Genetic Research, Massachusetts General Hospital (MGH), Boston, MA.
Dajiang J LiuDepartment of Public Health Sciences, Institute of Personalized Medicine, Penn State College of Medicine, Hershey, PA.
Alison M AyresCenter for Human Genetic Research, Massachusetts General Hospital (MGH), Boston, MA.
Joshua N GoldsteinDepartment of Emergency Medicine, MGH, Boston, MA.
Anand ViswanathanJ. Philip Kistler Stroke Research Center, Department of Neurology, MGH, Boston, MA.
Steven M GreenbergJ. Philip Kistler Stroke Research Center, Department of Neurology, MGH, Boston, MA.
Magdy SelimDepartment of Neurology, Beth Israel Deaconess Medical Center, Boston, MA.
James F MeschiaDepartment of Neurology, Mayo Clinic, Jacksonville, FL.ORCID 0000-0002-4475-8142
Devin L BrownStroke Program, Department of Neurology, University of Michigan Health System, Ann Arbor, MI.
Bradford B WorrallDepartments of Neurology and Public Health Sciences, University of Virginia Health System, Charlottesville, VA.
Scott L SillimanDepartment of Neurology, University of Florida College of Medicine, Jacksonville, FL.
David L TirschwellStroke Center, Harborview Medical Center, University of Washington, Seattle, WA.
Matthew L FlahertyDepartment of Neurology, University of Cincinnati College of Medicine, Cincinnati, OH.
Peter KraftDepartments of Epidemiology and Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA.
Jeremiasz M JagiellaDepartment of Neurology, Jagiellonian University Medical College, Krakow, Poland.
Helena SchmidtInstitute of Molecular Biology and Biochemistry, Medical University Graz, Graz, Austria.
Björn M HansenDivision of Neurology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
Jordi Jimenez-CondeNeurovascular Research Unit, Department of Neurology, Municipal Institute of Medical Investigation-Hospital of the Sea, Autonomous University of Barcelona, Barcelona, Spain.
Eva Giralt-SteinhauerNeurovascular Research Unit, Department of Neurology, Municipal Institute of Medical Investigation-Hospital of the Sea, Autonomous University of Barcelona, Barcelona, Spain.
Roberto ElosuaNeurovascular Research Unit, Department of Neurology, Municipal Institute of Medical Investigation-Hospital of the Sea, Autonomous University of Barcelona, Barcelona, Spain.
Elisa Cuadrado-GodiaNeurovascular Research Unit, Department of Neurology, Municipal Institute of Medical Investigation-Hospital of the Sea, Autonomous University of Barcelona, Barcelona, Spain.
Carolina SorianoNeurovascular Research Unit, Department of Neurology, Municipal Institute of Medical Investigation-Hospital of the Sea, Autonomous University of Barcelona, Barcelona, Spain.
Koen M van NieuwenhuizenDepartment of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.ORCID 0000-0002-4815-002X
Catharina J M KlijnDepartment of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
Kristiina RannikmaeDivision of Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Neshika SamarasekeraDivision of Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Rustam Al-Shahi SalmanDivision of Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Catherine L SudlowDivision of Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Ian J DearyCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom.
Andrea MorottiDepartment of Clinical and Experimental Sciences, Neurology Clinic, University of Brescia, Brescia, Italy.
Alessandro PezziniDepartment of Clinical and Experimental Sciences, Neurology Clinic, University of Brescia, Brescia, Italy.
Joanna PeraDepartment of Neurology, Jagiellonian University Medical College, Krakow, Poland.
Andrzej UrbanikDepartment of Neurology, Jagiellonian University Medical College, Krakow, Poland.
Alexander PichlerDepartment of Neurology, Medical University of Graz, Graz, Austria.
Christian EnzingerDepartment of Neurology, Medical University of Graz, Graz, Austria.
Bo NorrvingDivision of Neurology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
Joan MontanerNeurovascular Research Laboratory and Neurovascular Unit, Research Institute, Vall d'Hebron Hospital, Autonomous University of Barcelona, Barcelona, Spain.
Israel Fernandez-CadenasNeurovascular Research Laboratory and Neurovascular Unit, Research Institute, Vall d'Hebron Hospital, Autonomous University of Barcelona, Barcelona, Spain.
Pilar DelgadoNeurovascular Research Laboratory and Neurovascular Unit, Research Institute, Vall d'Hebron Hospital, Autonomous University of Barcelona, Barcelona, Spain.
Jaume RoquerNeurovascular Research Unit, Department of Neurology, Municipal Institute of Medical Investigation-Hospital of the Sea, Autonomous University of Barcelona, Barcelona, Spain.
Arne LindgrenDivision of Neurology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
Agnieszka SlowikDepartment of Neurology, Jagiellonian University Medical College, Krakow, Poland.
Reinhold SchmidtDepartment of Neurology, Medical University of Graz, Graz, Austria.
Chelsea S KidwellDepartment of Neurology, University of Arizona, Tucson, AZ.
Steven J KittnerDepartment of Neurology, Baltimore Veterans Administration Medical Center and University of Maryland School of Medicine, Baltimore, MD.
Salina P WaddyNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
Carl D LangefeldCenter for Public Health Genomics and Department of Biostatistical Sciences, Wake Forest University, Winston-Salem, NC.
Goncalo AbecasisCenter for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI.
Cristen J WillerDivision of Cardiology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI.
Sekar KathiresanCenter for Human Genetic Research, Massachusetts General Hospital (MGH), Boston, MA.
Daniel WooDepartment of Neurology, University of Cincinnati College of Medicine, Cincinnati, OH.
Jonathan RosandCenter for Human Genetic Research, Massachusetts General Hospital (MGH), Boston, MA.
Global Lipids Genetics Consortium and International Stroke Genetics Consortium
Broad Institute · USUniversitat Autònoma de Barcelona · ESJagiellonian University · PLMedical University of Graz · ATUniversity of Edinburgh · GBLund University · SEUniversity of Michigan · USPhilips (United States) · USUniversity of Brescia · ITUniversity of Cincinnati Medical Center · USBeth Israel Deaconess Medical Center · USHarvard University · USInstitute of Genetics and Cancer · GBJacksonville College · USMassachusetts General Hospital · USMGH Institute of Health Professions · USNational Institutes of Health · USPennsylvania State University · USRadboud University Nijmegen · NLUniversity Medical Center Utrecht · NL
Funding
Ethnic/Racial Variation in Intracerebral Hemorrhage (ERICH)U01NS069763 · NINDS · UNIVERSITY OF CINCINNATI · PI ANDERSON, CHRISTOPHER DAVID, DEMEL, STACIE · 2010 to 2024
$34.2MSTROKE INCIDENCE AND OUTCOME AMONG BLACKS AND WHITESR01NS030678 · NINDS · UNIVERSITY OF CINCINNATI · PI KISSELA, BRETT M, KLEINDORFER, DAWN O · 1993 to 2024
$26.7MSpecialized Programs of Translational Research in Acute Stroke at the PartnersP50NS051343 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI SCHWAMM, LEE H · 2006 to 2013
$17.5MGenetic&Environment Risk Factors for Hemorrhagic StrokeR01NS036695 · NINDS · UNIVERSITY OF CINCINNATI · PI WOO, DANIEL · 1997 to 2012
$14.1MVascular Dysfunction in Cerebral Amyloid AngiopathyR01AG026484 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI GREENBERG, STEVEN M · 2005 to 2019
$7.5MUsing genetic variation to study biology of blood lipids & coronary heart diseaseR01HL127564 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Pradeep Natarajan, Gina Marie Peloso · 2015 to 2026
$7.3MGenetic and Environmental Risk Factors for Hemorrhagic StrokeU01NS036695 · NINDS · UNIVERSITY OF CINCINNATI · PI ROSAND, JONATHAN, WOO, DANIEL · 2016 to 2020
$7.0MGene Discovery for Warfarin-Related Intracerebral HemorrhageR01NS059727 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI ROSAND, JONATHAN · 2008 to 2012
$4.2MMethod to Enhance the Rare Variant Genetic Architecture Analysis in Meta-AnalysesR01HG008983 · NHGRI · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI LIU, DAJIANG · 2016 to 2019
$1.6MMolecular Neuroimaging of Disease Mechanisms in Cerebral Amyloid AngiopathyK23NS083711 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI GUROL, MAHMUT EDIP · 2014 to 2018
$988kGenetic Analyses of Lipids in Cerebral Hemorrhage and Small Vessel DiseaseK23NS086873 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI ANDERSON, CHRISTOPHER DAVID · 2014 to 2018
$951kMedical Research Council G0900428Medical Research Council G1002605Medical Research Council MR/K026992/1Medical Research Council MR/M013111/1NHGRI NIH HHS R01 HG008983NHLBI NIH HHS R01 HL127564NIA NIH HHS R01 AG026484NINDS NIH HHS K23 NS083711NINDS NIH HHS K23 NS086873NINDS NIH HHS L30 NS084073NINDS NIH HHS P50 NS051343NINDS NIH HHS R01 NS030678NINDS NIH HHS R01 NS036695NINDS NIH HHS R01 NS059727NINDS NIH HHS U01 NS036695NINDS NIH HHS U01 NS069763
Abstract
objectiveIn observational epidemiologic studies, higher plasma high-density lipoprotein cholesterol (HDL-C) has been associated with increased risk of intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl ester transfer protein (CETP) gene activity increase plasma HDL-C; as such, medicines that inhibit CETP and raise HDL-C are in clinical development. Here, we test the hypothesis that CETP DNA sequence variants associated with higher HDL-C also increase risk for ICH.
methodsWe performed 2 candidate-gene analyses of CETP. First, we tested individual CETP variants in a discovery cohort of 1,149 ICH cases and 1,238 controls from 3 studies, followed by replication in 1,625 cases and 1,845 controls from 5 studies. Second, we constructed a genetic risk score comprised of 7 independent variants at the CETP locus and tested this score for association with HDL-C as well as ICH risk.
resultsTwelve variants within CETP demonstrated nominal association with ICH, with the strongest association at the rs173539 locus (odds ratio [OR] = 1.25, standard error [SE] = 0.06, p = 6.0 × 10
interpretationGenetic variants in CETP associated with increased HDL-C raise the risk of ICH. Given ongoing therapeutic development in CETP inhibition and other HDL-raising strategies, further exploration of potential adverse cerebrovascular outcomes may be warranted. Ann Neurol 2016;80:730-740.
Indexed as
AdultAgedCerebral HemorrhageCholesterol Ester Transfer ProteinsCholesterol, HDLFemaleGenetic Predisposition to DiseaseGenotypeHumansMaleMiddle AgedPolymorphism, Single NucleotideCETP protein, humanCholesterol Ester Transfer ProteinsCholesterol, HDL
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